Nephropathy is a complication which is often seen in diabetes, as well with diabetes type 1, diabetes type 2, pre-diabetes, gestational as drug-induced diabetes. There are wide differences in estimates of how many people with diabetes will progress to having diabetic kidney disease—from 6 to 27 percent of people with Type 1 diabetes, to 25 to 50 percent of Type 2. Diabetic disease is characterized by high levels of blood glucose which is associated with tissue damage. Small vascular and capillary structures are very sensitive to diabetes-induced injury and organs such as the kidney are frequently affected. By endothelial and microvascular damage the kidneys start to become ‘leaky’ which is first diagnosed on basis of increased protein levels in the urine (microalbuminuria). If no intervention follows, this develops in an even higher level of proteins in the urine (macroalbuminuria), glucosuria and finally in end-stage renal disease (ESRD) which necessitates dialysis or kidney transplantation.
Diabetic nephropathy is the major cause of ESRD worldwide, and its incidence has increased by more than 50% in the past ten years (USRDS 2008 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the Unites States, NIH).
Similar micro- and macrovascular complications that play a role in renal damage also can result in other forms of complications, such as retinopathy. Is is likely that micro- and macrovascular dysfunction also play a role in the development other diabetes-associated pathologies such as neuropathy, hepatopathy, hepatosteatosis, adipose inflammation (e.g. in visceral adiposity) and pancreas dysfunction.
Lack of reliable, translational animal models that sufficiently mimic the multifactorial human pathofysiology have prevented optimal development of insight in the disease mechanism and candidate therapy/drug development. Therefore, much effort has been devoted to develop animal models for this specific complication in diabetes (see: Brosius, F. C. et al., 2009, J. Am. Soc. Nephrol. 20:2503-2512). Some mouse models have been described in this overview, but it is considered that there is still need for more, and/or more comprehensive animal models. Some of the drawbacks of the present models are: i) that diabetic complications develop heterogeneously with great variations between animals (despite comparable genetic make-up and age) and ii) that the severity of diabetic complications, especially microalbuminuria, does not progress over time as it is the case in humans.